DESCRIPTION: Following spinal cord injury, secondary injury and the formation of a glial scar create an environment that does not foster axonal regeneration. Therefore, those sustaining spinal cord injury have some form of functional deficit below the level of injury. With increasing frequency, scientists and engineers are developing biomaterial scaffolds to help promote axonal regeneration into and through the lesion site. While no biomaterial strategy is used clinically, several strategies show promise within animal models of spinal cord injury. Recently, our group discovered that electrospun fiber scaffolds are able to facilitate robust regeneration of axons within a complete transection spinal cord injury model. Results from this study also demonstrated that astrocytes migrated extensively into the biomaterial conduct, instead of forming the typical glial scar that surrounds the lesion site. In this application, we seek to bettr understand astrocytic response to topography and uncover the possible mechanisms by which topographically changed astrocytes facilitate neuroprotection and axonal regeneration following acute spinal cord injury. Aims 1 and 2 of the application attempt to elucidate how astrocytes are phenotypically changed by fibers and if these phenotypic changes are altered by motor neuron presence. Additionally, we will examine the ability of these astrocytes to protect neurons from glutamate excitotoxicity. Lastly, in Aim 3, we will employ electrospun fibers within hemisection and contusive models of rat, acute SCI and examine astrocyte phenotypic changes, neuroprotective benefits and the ability of electrospun fibers to promote spinal cord regeneration and functional recovery. In conclusion, understanding the mechanisms by which biomaterials change astrocytes, in ways that support axonal regeneration, may lead to development of a biomaterial treatment option for those who suffer from acute spinal cord injury.